Disease relevance of o-Arsanilic acid

• The histologic similarity to chronic inorganic arsenical poisoning, in which angiosarcomas also occur, and to idiopathic portal hypertension (Banti's syndrome) suggests that the latter syndrome at times results from unknown toxic, possible environmental, chemicals [1].
• The melaminophenyl arsenical melarsoprol is still used to treat African sleeping sickness, a disease caused by parasitic protozoa of the Trypanosoma brucei subgroup [2].
• Locking the CD4 and the thioredoxin active-site dithiols in the reduced state with a hydrophilic trivalent arsenical blocked entry of HIV-1 into susceptible cells [3].
• Noncirrhotic presinusoidal portal hypertension associated with chronic arsenical intoxication [4].
• Arsenical air pollution and lung cancer [5].

Psychiatry related information on o-Arsanilic acid

• The latency periods for the development of arsenical keratoses, Bowen's disease, and SCC were 28, 39, and 41 years, respectively [6].

High impact information on o-Arsanilic acid

• In vitro, the MRPs can collectively confer resistance to natural product drugs and their conjugated metabolites, platinum compounds, folate antimetabolites, nucleoside and nucleotide analogs, arsenical and antimonial oxyanions, peptide-based agents, and, under certain circumstances, alkylating agents [7].
• Arsenical-resistant trypanosomes lack an unusual adenosine transporter [2].
• A significant 19th century public health problem was that the inhabitants of many houses containing wallpaper decorated with green arsenical pigments experienced illness and death [8].
• The patient had taken an arsenical preparation during a period of 12 yr because of psoriasis and subsequently developed keratotic changes of the palms and soles of his feet and an epithelioma of the scrotum [4].
• To examine the role of PML in mediating arsenical activity, we also tested these agents using murine embryonic fibroblasts (MEFs) and bone marrow (BM) progenitors in which the PML gene had been inactivated by homologous recombination [9].

Chemical compound and disease context of o-Arsanilic acid

• The patients with arsenical or vinyl chloride exposure could not be differentiated from the other three patients with idiopathic portal hypertension [10].
• The ArsC protein encoded by the arsenical resistance operon of plasmid R773 catalyzes the reduction of arsenate to arsenite in Escherichia coli [11].
• These results suggest that combinations of DFMO and suramin should be examined clinically for activity in arsenical-drug-refractory cases of East African sleeping sickness [12].
• This has been clearly demonstrated in the case of the melamine-based arsenical and the diamidine classes of drug that are already in use in the treatment of human African trypanosomiasis [13].
• Among the environmental factors associated with STS are external radiation therapy, Thorotrast, arsenical pesticides and medications, phenoxyherbicides, dioxin, vinyl chloride, immunosuppressive drugs, alkylating agents, androgen-anabolic steroids, human immunodeficiency virus, and human herpes virus type 8 [14].

Biological context of o-Arsanilic acid

• We have investigated the effects of the organic arsenical, melarsoprol (a drug used for treatment of trypanosomiasis), upon induction of apoptosis in cell lines representative of chronic B-cell lymphoproliferative disorders [15].
• They further demonstrate that the multidrug resistance phenotype conferred by MRP is similar but not identical to that conferred by P-glycoprotein and includes resistance to arsenical and antimonial oxyanions [16].
• The products of the arsenical resistance operon of resistance plasmid R733 form an efflux system for arsenicals [17].
• The ArsA ATPase is the catalytic subunit of the Ars pump that catalyzes arsenical extrusion in Escherichia coli, thus providing resistance [18].
• Nucleotide sequence of the structural genes for an anion pump. The plasmid-encoded arsenical resistance operon [19].

Anatomical context of o-Arsanilic acid

• Both pokeweed mitogen-induced normal plasma cells and malignant plasma cells showed a normal nuclear distribution of PML protein, which was disrupted by As2O3 but not by melarsoprol, suggesting that the two arsenical derivatives acted by different mechanisms [20].
• In nonseparated bone marrow samples, both arsenical compounds triggered death in myeloma cells while sparing most myeloid cells, as demonstrated by double staining with annexin V and CD38 or CD15 antibodies [20].
• The effects of the trivalent arsenical phenylarsine oxide (PAO) on the activity of NADPH oxidase in human neutrophils were studied [21].
• Phenylarsine oxide (PAO), a trivalent arsenical that interacts with vicinal dithiols, is most potent in inducing rapid shedding of L-selectin from isolated neutrophils, eosinophils, and lymphocytes as well as from neutrophils in whole blood [22].
• The residual coupling activity of depleted submitochondrial particles was highly resistant to cadmium or arsenical [23].

Associations of o-Arsanilic acid with other chemical compounds

• The synthetic tripeptide arsenical 4-(N-(S-glutathionylacetyl)amino)p-phenylarsenoxide (p-GSAO) is an angiogenesis inhibitor that inactivates mitochondrial adenine nucleotide translocase (ANT) by cross-linking a pair of matrix-facing cysteine residues [24].
• In our studies of the effects of the trivalent arsenical phenylarsine oxide on insulin-dependent hexose uptake in 3T3-L1 adipocytes, we needed direct methods to study arsenical-protein interactions [25].
• Phospho-422(aP2) protein (pp15) accumulates in cells treated with insulin and PAO because the arsenical blocks turnover of the phosphoryl group of pp15 [26].
• It seems therefore that selection for resistance to either pentamidine or arsenical drugs can result in a similar phenotype of reduced drug accumulation, explaining the occurrence of cross-resistance [27].
• We also show that a laboratory line of Trypanosoma brucei gambiense, adapted to high levels of resistance for the melaminophenyl arsenical drug melarsamine hydrochloride (Cymelarsan), had similarly lost TbAT1 and HAPT1 activity while retaining LAPT1 activity [27].

Gene context of o-Arsanilic acid

• In Saccharomyces cerevisiae, expression of the ACR2 and ACR3 genes confers arsenical resistance [28].
• In addition, these inhibitory effects on bFGF- or VEGF-stimulated cell proliferation suggest antiangiogenic potential of these arsenical compounds [29].
• This strong cytotoxicity of an inorganic arsenical, arsenite, might be mediated via active oxygen and protease activation because it was inhibited by the addition of some antioxidant reagents, such as superoxide dismutase (SOD), catalase, and GSH, or by a peptide inhibitor of interleukin-1 beta-converting enzyme (ICE) [30].
• The hypothetical product of the ACR3 gene shows high similarity to the hypothetical membrane protein encoded by Bacillus subtilis ORF1 of the skin element and weak similarity to the ArsB membrane protein of the Staphylococcus aureus arsenical-resistance operon [31].
• These findings suggest that all three novel genes: ACR1, ACR2 and ACR3 are involved in the arsenical-resistance phenomenon in S. cerevisiae [31].

Analytical, diagnostic and therapeutic context of o-Arsanilic acid

• Thus, it is suggested that in this patient, presinusoidal portal hypertension was secondary to chronic arsenical intake associated with marked intrahepatic vascular changes seen on portography [4].
• Melaminophenyl arsenical drugs are a mainstay of chemotherapy against late-stage African sleeping sickness, but drug resistance is increasingly prevalent [32].
• Crystallization and preliminary X-ray diffraction analysis of the ArsC protein from the Escherichia coli arsenical resistance plasmid, R773 [33].
• Epidemiologic studies demonstrated that long-term exposure to arsenic induces arsenical skin cancers, including Bowen's disease [34].
• The new synthetic, more potent and less calcemic analogs might find wide application in chemotherapy of premalignant and early malignant cutaneous tumors and could be especially useful for chemoprevention in the high-risk groups, e.g., xeroderma pigmentosum, organ transplant recipients, arsenical keratoses and others [35].

References